Autologous Tumor Lysate-pulsed Dendritic Cell Immunotherapy for Pediatric Patients with Newly Diagnosed or Recurrent High-grade Gliomas

摘要: Brain tumors are the second most common malignancy in children and a leading cause of morbidity mortality from childhood cancers (1). Great strides treatment brain have been made over last several decades due to more advanced neurosurgical techniques, which allow for complete safer resection, advances delivery chemotherapy radiation therapy (2–4). However, little progress was certain types tumors, notably malignant gliomas, brainstem that recurred after standard (5–7). In addition, although surgery, therapy, can result long term survival some pediatric patients with these suffer myriad late effects, including serious cognitive endocrine dysfunction, renal cardiac disease, as well malignancies (8–11). Thus, there is an urgent need targeted, less toxic, effective therapies this population. Immunotherapy has gained recent attention targeted toxic approach cancer treatment, tumors. Recent successes using immunotherapy against prostate cancer, melanoma, cell carcinoma prompted increased interest also establishing methods (12–14). A number different immunotherapeutic methodologies attempted regards tumor radioisotope-conjugated passive antibodies, peptide based vaccines, DC-based vaccines (15). DCs regarded potent antigen-presenting cells humans. They able handle variety antigenic mediums, peptides, whole proteins, RNA DNA, they process display peptides on their surface context major histocompatibility complex (MHC) class I or II molecules. Stimulation by even protein lysates, allows cross-stimulation cytotoxic T-cell responses, T-helper (Th)1 Th2 pathways (16, 17), would theoretically be than trying stimulate immunity MHC restricted alone. Several clinical trials conducted DCbased but only two involved (16). first series, Caruso colleagues used RNA-pulsed vaccine nine concluded it safe feasible (18). Ardon co-authors recently lysate-pulsed 45 recurrent (33 high-grade HGG) reported 6 HGG had lasting greater 24 months. Five out six received additional (19). Here, we report single-institution pilot trial DC primary HGG.